الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Breast cancer remains an important worldwide health concern as a major cause of
morbidity and mortality among females.
Ongoing researches have been conducted to identify new markers that could help in
accurate prediction of breast cancer outcome besides the conventionally used prognostic
factors and can serve as a possible target for treatment. Among them, FOXA1 and FOXM1
have been proposed as potential biomarkers.
The objective of this work is to determine the expression pattern of FOXA1 and
FOXM1 in specimens of invasive mammary carcinomas in correlation with other
recognized clinicopathological parameters to ascertain their potential applicability as a
predictor of tumor behavior.
Histological examination and IHC staining of 100 invasive breast carcinoma
specimens (ductal and lobular) with ER, PR, HER2, FOXA1, and FOXM1, were performed.
This study enrolled 100 cases of invasive breast cancer with a mean age of 55.77. Of
the 100 specimens examined, 75 tumors (75%) were IDC NST whereas 25 (25%) were of
invasive lobular type. Thirty-six of the tumors were T1, 53 tumors were T2 and 11 tumors
were T3. Grade I tumors represent about 4% of the tumors while grade II and grade III
were 72% and 24% respectively. Forty-three of the studied cases (43%) had metastatic LN
while 48 (48%) cases had tumors with positive LVI. ER/PR positivity was detected in 64%
of tumors whereas HER2 overexpression was detected in 28% of tumors.
FOXA1 expression was significantly higher in low grade tumors (p=0.0001), ER/PR
expressing tumors (p=0.0001), HR+/HER2–group and HR+/HER2+group (p =0.0001), while
it showed no significant association with HER2 status (p=0.377), LVI (p=0.077) and LN
status (p=0.152).
Although FOXM1 failed to show association with tumor grade (p=0.656), its
expression showed a significant correlation with positive LVI (p=0.02), presence of LN
metastases (p=0.02), ER/PR negative tumors (p=0.0001), HER2 expressing tumors (p =
0.04), HR–/HER2+ subtype and TNBC (p=0.0001).
Both FOXA1 and FOXM1 failed to show significant association with tumors size
(p= 0.28 and 0.173 respectively) and histologic type (p=0.414 and 0.411 respectively).
When we assessed tumor recurrence status in a subset of HR-positive breast cancers
(58/64), upregulation of FOXM1 expression and downregulation of FOXA1 expression
were significantly associated with the development of tumor recurrence (p = 0.015 and
0.009 respectively).
In the present study, FOXA1 and FOXM1 showed a reverse correlation suggesting
their different and somehow opposing roles in breast cancer (p=0.001).
FOXA1 expression defines cases with better tumor features while FOXM1 correlates
with a more aggressive form of breast cancer. FOXA1 and FOXM1 expression could serve as
useful predictors of breast cancer behavior besides conventionally used prognostic factors.
Summary, Conclusions and Recommendations
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6.2. Conclusions
o Positive expression of FOXA1 correlates with favorable tumor characteristics such
as well-differentiated histology and ER/PR positivity whereas FOXM1
overexpression is associated with a more aggressive phenotype characterized by the
presence of LN involvement, positive LVI, ER/PR negativity, and HER2
overexpression. A significant increase of FOXA1 expression was observed in HR
expressing tumors compared to HR–/HER2+ tumors and TNBC while FOXM1 was
significantly higher in HER2 expressing tumors and TNBC.
o Upregulation of FOXM1 expression and downregulation of FOXA1 expression are
significantly correlated with the development of tumor recurrence.
o The reverse correlation between FOXA1 and FOXM1 expression could verify their
opposing role in breast cancer development.
6.3. Recommendations
o Studying the expression of FOXA1 and FOXM1 on a large scale with the inclusion
of other histologic types to confirm the present results and ascertain their role in
carcinogenesis and disease progression.
o Further studies with adequate follow up period, not only for HR- positive tumors but
also for HER2 expressing tumors and TNBC, are recommended to assess the relation
between FOXA1 and FOXM1 expression and response to therapy among different
breast cancer subtypes.
o Further exploration of the prognostic potential of FOXA1 and FOXM1 in clinical
trials is required to evaluate whether they should be included in routine immune
panels as additional support for oncologists in determining the possible therapeutic
choices for the patients.
o Future studying of FOXA1 and FOXM1, not only as prognostic markers but also as
therapeutic targets.